clinical trial of wbc100 capsule in relapsed/refractory acute myeloid leukemia

Conditions: AML (Acute Myelogenous Leukemia; Relapsed Acute Myelogenous Leukemia; Refractory Acute Myeloid Leukemia; Hematologic Malignancy; C-Myc; Adult Acute Myeloid Leukemia

Summary: the goal of this clinical trial is to evaluate the safety, tolerability, pharmacokinetics (pk), and preliminary efficacy of wbc100 capsules in patients with relapsed or refractory acute myeloid leukemia (r/r aml). the main questions it aims to answer are: * what is the safety and tolerability profile of wbc100 in r/r aml patients? * can wbc100 effectively induce remission in r/r aml patients? participants will: * take wbc100 capsules orally once daily in 28-day treatment cycles; * undergo regular safety assessments, including adverse event monitoring and laboratory tests; * provide blood samples for pharmacokinetic (pk) analysis; * have their remission status and efficacy evaluated according to the eln2022 criteria.


Eligibility criteria:
inclusion criteria: * 1. signed informed consent and compliance with study procedures; * 2. male or female participants aged ≥18 years at the time of consent; * 3. diagnosis of relapsed or refractory acute myeloid leukemia (r/r aml) according to the 2016 world health organization (who) classification; * 4. ecog ps 0-2; * 5. life expectancy ≥3 months; * 6. adequate bone marrow reserve and organ function as defined below: 1. bone marrow reserve: peripheral wbc \< 25 × 10⁹/l (leukocyte-reducing agents are allowed, with a washout period of at least 5 half-lives prior to study drug administration); 2. coagulation: international normalized ratio (inr) ≤ 2; 3. hepatic function: total bilirubin (tbil) ≤ 1.5 × uln; alt and ast ≤ 2.5 × uln. in cases of hepatic involvement: alt or ast ≤ 5 × uln, and tbil ≤ 3 × uln; 4. renal function: creatinine clearance ≥60 ml/min (cockcroft-gault), or serum creatinine ≤1.5 × uln; 5. cardiac function: left ventricular ejection fraction (lvef) ≥50%; qtcf ≤450 ms for males, ≤470 ms for females. * 7. female participants of childbearing potential and fertile male participants with partners of childbearing potential must use medically approved contraception during treatment and for 6 months after the final dose. exclusion criteria: * 1. known hypersensitivity to wbc100 capsules or any of their excipients; * 2. diagnosis of acute promyelocytic leukemia (apl); * 3. diagnosis of mixed phenotype acute leukemia, chronic myeloid leukemia in blast crisis, or aml transformed from myelodysplastic syndromes (mds) or myeloproliferative neoplasms (mpn); * 4. subjects with relapse after allogeneic hsct, grade ≥ 2 acute gvhd, extensive chronic gvhd requiring immunosuppressive therapy, or autologous hsct within the past 90 days; * 5. subjects who have undergone major surgery, have active ulcers, or have unhealed wounds within 28 days prior to the first dose; * 6. received other investigational drugs or treatments within 28 days prior to the first administration, or are still within the safety follow-up period of another clinical trial; * 7. subjects with a history of severe cardiovascular or cerebrovascular conditions, including but not limited to: 1. significant arrhythmias or conduction disorders (e.g., ventricular arrhythmias, grade ii-iii av block); 2. thromboembolic events requiring anticoagulation or presence of vena cava filter; 3. nyha class iii-iv heart failure; 4. poorly controlled hypertension (sbp ≥140 mmhg or dbp ≥90 mmhg despite treatment). * 8. evidence of severe or uncontrolled systemic diseases, such as refractory effusions, poorly controlled diabetes, or significant disorders of the psychiatric, neurological, cardiovascular, respiratory, endocrine, gastrointestinal, hepatic, or renal systems; * 9. history or presence of immunodeficiency, autoimmune disease requiring systemic immunosuppressants, or organ transplantation; * 10. congestive heart failure, aortic dissection, stroke (excluding lacunar infarct), unstable angina, myocardial infarction, bypass surgery, or pulmonary embolism within 180 days prior to first dosing; * 11. known risk factors for qt prolongation, including congenital long qt syndrome or drug-induced arrhythmia history; * 12. positive for syphilis antibodies, hiv, active hbv infection (hbsag+ or hbcab+ with hbv dna ≥1000 iu/ml), or active hcv infection (hcv ab+ with detectable hcv rna); * 13. active infection requiring systemic treatment, including uncontrolled bacterial, viral, or fungal infections; * 14. gastrointestinal conditions preventing oral drug intake or absorption, such as severe vomiting, chronic diarrhea, intestinal stoma, malabsorption, or inability to swallow; * 15. use of strong cyp450 inhibitors/inducers that cannot be stopped ≥7 days before dosing; * 16. receipt of monoclonal antibodies, adcs, radiotherapy within 28 days (14 days for localized radiotherapy), cytotoxic chemotherapy, targeted small molecules within 14 days or 5 half-lives, or car-t therapy within 100 days; * 17. receipt of any live or attenuated vaccines (e.g., influenza, varicella) within 28 days; * 18. history of other malignancies within 2 years, except adequately treated basal cell carcinoma, carcinoma in situ of cervix or breast, or squamous cell carcinoma of the skin; * 19. history of psychiatric or neurological disorders that may interfere with protocol compliance; * 20. inability to tolerate venous blood draws; * 21. pregnant or breastfeeding women, or women with positive serum hcg during screening; * 22. any condition deemed by the investigator to make the subject unsuitable for study participation.

Keywords: c-myc molecular glue acute myelogenous leukemia relapsed and refractory acute myelogenous leukemia